AK-1780

iStock, JHVEPhoto Before being discontinued, the P2X7 receptor blocker had cleared a master protocol study in chronic pain, though Eli Lilly said that results were not sufficient for advancement of the Asahi Kasei–partnered asset. Lilly has halted work on another mid-stage pain asset as the pharma continues to find its footing in the analgesic arena. The drug, named LY3857210, is an orally available inhibitor of the P2X7 receptor that is found on a variety of immune cells and considered a key player in chronic pain pathology. Before being discontinued, the drug had completed a Phase II master protocol study covering chronic low back pain , osteoarthritis pain and diabetic peripheral neuropathic pain . In a statement to Fierce Biotech , a spokesperson for Lilly said that data from LY3857210’s development “did not meet our high internal bar for success.” Still, the pharma is “assessing next steps for the program, including possible additional indications.” LY3857210 came to Lilly in early 2021, when it paid $20 million upfront —and promised up to $210 million in milestones—to partner with Japan’s Asahi Kasei and license the drug, then called AK1780. Despite ending LY3857210’s pain run, this partnership is still ongoing, a spokesperson for the Asahi Kasei told Fierce . This is the second mid-stage pain asset that Lilly has dumped in recent months, with the pharma discarding the Phase II oral SSTR4 agonist mazisotine in August. Prior to its discontinuation, mazisotine had also completed a chronic pain master protocol study, testing its safety and efficacy in osteoarthritis , low back pain and diabetic peripheral neuropathic pain . Despite culling two investigational analgesics, Lilly continues to invest in its pain pipeline. In May this year, for instance, the pharma swallowed SiteOne Therapeutics in a deal that could hit $1 billion in value, gaining access to its non-opioid pain drugs. The star of that agreement is STC-004, a Nav1.8 blocker that according to Lilly’s Q3 presentation on Thursday is still in Phase I development. In a May 27 note, analysts at BMO Capital markets said that the deal will help Lilly position itself for “diversification and growth beyond GLP-1s.” Lilly is also working on other pain meds, including one Phase I AT2R blocker and an anti-epiregulin antibody in mid-stage development. In addition, the pharma is positioning its closely watched oral obesity asset orforglipron for knee osteoarthritis pain. The drug is currently in late-stage studies for this indication, with study completion expected in 2027. These pipeline changes on Thursday were vastly overshadowed by Lilly’s financial results , with the pharma claiming that its blockbuster weight-loss franchise tirzepatide finally unseated Merck’s cancer behemoth Keytruda as the top-selling drug in the world. In the third quarter, sister brands Mounjaro and Zepbound together raked in $10.1 billion worldwide, while Keytruda trailed with $8.1 billion in Q3 earnings. All told, Lilly reported an eye-watering $17.6 billion in the third quarter.